Inhibition of perilipin 2 attenuates cerebral ischemia/reperfusion injury by blocking NLRP3 inflammasome activation both in vivo and in vitro.

Cerebral ischemia/reperfusion (CI/R) usually causes neuroinflammation within the central nervous system, further prompting irreversible cerebral dysfunction. Perilipin 2 (Plin2), a lipid droplet protein, has been reported to exacerbate the pathological process in different diseases, including inflammatory responses. However, the role and mechanism of Plin2 in CI/R injury are unclear. In this study, the rat models of transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R) were established to mimic I/R injury, and we found that Plin2 was highly expressed in the ischemic penumbra of tMCAO/R rats. The siRNA-mediated knockdown of Plin2 significantly decreased neurological deficit scores and reduced infarct areas in rats induced by I/R. Detailed investigation showed that Plin2 deficiency alleviated inflammation of tMCAO/R rats as evidenced by reduced secretion of proinflammatory factors and the blockade of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. In vitro experiments showed that Plin2 expression was upregulated in mouse microglia subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Plin2 knockdown inhibited OGD/R-induced microglia activation and the accumulation of inflammation-related factors. Taken together, this study demonstrates that lipid droplet protein Plin2 contributes to the pathologic process of CI/R damage by impacting inflammatory response and NLRP3 inflammasome activation. Thus, Plin2 may provide a new therapeutic direction for CI/R injury.

The Prognostic Value of the THRIVE Score, the iScore Score and the ASTRAL Score in Chinese Patients With Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) has a higher morbidity and mortality rate. Many prediction tools have been developed to predict the risk of poor outcomes in patients after AIS, such as the THRIVE score, the iScore score, and the ASTRAL score. However, the predictive value of above 3 prediction tools in Chinese patients with AIS need to be further verified. So, this study aimed to determine the ability of the THRIVE score, the iScore score, and the ASTRAL score in predicting clinical poor outcomes in Chinese patients with AIS at 1 year. METHODS: A total of 772 patients with AIS were included in this study. The baseline data of all patients were collected. The THRIVE score, the iScore score, and the ASTRAL score were calculated. All patients were followed up at 1 year. The poor outcome was defined as death, moderate/severe disabilities (modified Rankin scale, mRS > 2), most severe disability (mRS ≥ 5). Model discrimination was quantified by calculating the area under the receiver operating characteristic curve (AUC). The calibration was assessed using Hosmer-Lemeshow goodness-of-fit test and Pearson correlation coefficient. RESULTS: We identified 576 (74.6%) patients with good prognosis and 196 (25.4%) patients with poor prognosis. AUC values of THRIVE score in predicting 1-year poor prognosis was lower than the iScore score and the ASTRAL scores (P < .05). The chi-square values of Hosmer-Lemeshow for the 3 prediction tools were 2.114, 4.877, 5.838 (all P < .05), respectively. There was a high correlation between the observed and the expected poor prognosis (Pearson correlation coefficient, .985, .693, and .620; all P < .05). AUC values of THRIVE score in predicting 1-year mortality and severe disability were lower than the iScore scores (all P < .05). CONCLUSIONS: The iScore score and the ASTRAL score reliably predict 1-year poor outcomes in Chinese patients with AIS, and the iScore score can accurately predict 1-year mortality and severe disability in Chinese AIS patients.

Proton Magnetic Resonance Spectroscopy Study on the Metabolism Changes of Cerebellum in Patients with Post-Stroke Depression.

OBJECTIVE: To study the metabolic changes of cerebellum by proton magnetic resonance Spectroscopy (1H-MRS) and discuss the relationships between the cerebellar changes and depression severity in patients with post-stroke depression. METHODS AND RESULTS: Data of demographic characteristics, individual history and life style of all subjects were collected. 40 patients with stroke and 20 controls were enrolled. All groups received T1WI, T2WI, DWI and 1H-MRS examination. The cerebral infarction volume and the distribution and severity of leukoaraiosis were evaluated. The ratios of NAA/Cr, Cho/Cr and Cho/NAA in the cerebellum were calculated. There were no statistical significant difference in the NAA/Cr, Cho/Cr and Cho/NAA ratios in bilateral cerebellum between CONT group and NORM group. The Cho/Cr and Cho/NAA ratios in the cerebellum contralateral to the stroke region were higher in PSD group than those in NORM and CONT groups, and the Cho/Cr and Cho/NAA ratios in the cerebellum ipsilateral to the stroke region were similar with those in NORM and CONT groups. However, there were no statistical significant difference in the NAA/Cr ratios in bilateral cerebellum among three groups. CONCLUSION: The result shows preliminarily that the cerebellum involves in the development of post-stroke depression.

Cerebellar Fastigial Nucleus Electrical Stimulation Alleviates Depressive-Like Behaviors in Post-Stroke Depression Rat Model and Potential Mechanisms.

OBJECTIVE: To identify the molecular mechanism of post-stroke depression (PSD), and observe the therapeutic effects of cerebellar fastigial nucleus electrical stimulation (FNS) on the behaviors and regional cerebral blood flow (rCBF) in a PSD rat model. METHODS: Healthy SD rats were randomly divided into four groups (sham, stroke, post-stroke depress and FNS group). Sham group (n = 6) underwent sham operation. The other three groups (n = 6*3) underwent MCAO. Rats were examined twice a week in open filed test. Moreover, neuroprotective effect on cerebellar Purkinje cells and expression of cytokines in hippocampal tissue were examined. RESULTS: The PSD group showed a significant weight loss, decreased consumption of sucrose water, reduced rearing and locomotor activities. The FNS significantly alleviates the body weight loss and sucrose preference, locomotor and rearing activities. The bilateral rCBF was also restored after FNS treatment. Moreover, FNS improved the neuroprotection via suppressing apoptosis of cerebellar Purkinje cells. And the inflammatory cytokines mRNA level in hippocampus was significantly decreased. CONCLUSION: FNS treatment alleviates depressive-like behaviors and rCBF in PSD rats model, which could be attributed to its ability to protect cerebellar Purkinje cells and decrease the mRNA level of inflammatory cytokines.